What does rapamycin bind to?
Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase.
What does FK506 do?
FKBP12 is notable in humans for binding the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and patients with autoimmune disorders.
What does FKBP12 do?
FKBP12 functions as a cis/trans peptidyl prolyl isomerase (PPIase) that catalyzes interconversion between prolyl cis/trans conformations. Members of the FKBP family contain one or several PPIase domains, which do not always exhibit PPIase activity yet are all essential for their function.
What does FKBP stand for?
FKBP
| Acronym | Definition |
|---|---|
| FKBP | FK506 Binding Protein |
How does FK506 inhibit calcineurin?
Mode of action: Similar to cyclosporin A, FK506 blocks the activation of calcineurin through the formation of complexes with immunophilins. FK506 binds to an immunophilin called FK506 binding protein 12 (FKBP12), unlike cyclosporin A which binds to a different immunophilin [1].
What does the FKBP5 gene do?
The FKBP5 gene encodes a molecular co-chaperone of the glucocorticoid receptor complex, which modulates intracellular glucocorticoid signaling and plays an important role in homeostatic regulation of the stress response [42].
What is FRB protein?
FRB is a small domain derived from full length mTOR. In brief, rapamycin binds to a protein called FKBP12. Rapamycin bound to FKBP12 inhibits mTOR signaling.
How does rapamycin affect aging?
When taken late in life, rapamycin increases lifespan by 9-14% [155], despite the dosage being suboptimal [111]. This possibly equates to more than 7 years of human life. By comparison, smokers who quit late in life (at age 65 years), gain between 1.4 -3.7 years [172].
Is FK506 the same as tacrolimus?
Tacrolimus, formerly known as FK506, is a macrolide antibiotic with immunosuppressive properties.
What is FKBP5 methylation?
DNA methylation of the FKBP5 gene is assumed to alter FKBP5 expression and hence the synthesis of the FK506 binding protein 51, a central element of a genomic negative feedback loop for glucocorticoid receptor signaling.
Does rapamycin cause muscle loss?
The team, led by Professor Markus Rüegg, have discovered that mTORC1, which acts as a sensor and controls protein synthesis in the body, also contributes to sarcopenia and its suppression with the well-known drug rapamycin slows age-related muscle wasting.
What is FK506 binding protein?
FK506 binding proteins (FKBPs) are a large family of proteins that possess peptidyl prolyl cis/transisomerase (PPIase) domains. The founding member of this family is FKBP12, which is a 108 amino acid peptide containing the minimal sequence for a PPIase [1, 2].
Does PPIase bind to FK506?
The PPIase domain binds FK506 weakly in vitro. FKBP19 is highly expressed in the tumor tissue of hepatocellular carcinoma, suggesting that it may play a role in hepatic tumor development [144]. The other members of the ER FKBPs all contain two EF-hand motifs that bind to Ca2+.
What does FKBP51 do in prostate cancer?
FKBP51 has been found to associate androgen receptor (AR) and overexpression of FKBP51 stimulates AR transcriptional activity and cell proliferation [187]. In androgen independent prostate cancer cells, high level of FKBP51 is believed to sustain AR signaling in the absence of androgen [188].